Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets

In the paper

“suggesting that microglia play an essential role in AD development.”

What the sources say

• Supported

  The Background describes microglial networks as important in AD development and progression and says genetic studies implicate microglial function as a causal factor in late-onset AD. The Conclusion, under “What confers risk,” says studies suggest microglia play an active role in AD pathogenesis. These passages support the citing sentence’s suggested essential role, while acknowledging that the exact contribution remains uncertain. (LLM, conf=0.92)

  cites [124] Efthymiou, A. G. & Goate, A. M. Late onset Alzheimer’s disease genetics implicates microglial pathways in disease risk. Mol. Neurodegener. 12, 43 (2017). source

In the paper

“Microglial activation has also been detected by PET in patients with mild cognitive impairment (MCI).”

What the sources say

• Not checked yetcites [138] Fan, Z. et al. Influence of microglial activation on neuronal function in Alzheimer’s and Parkinson’s disease dementia. Alzheimers Dement. 11, 608–621.e607 (2015). source
• Not checked yetcites [139] Yasuno, F. et al. Increased binding of peripheral benzodiazepine receptor in mild cognitive impairment-dementia converters measured by positron emission tomography with [(1)(1)C]DAA1106. Psychiatry Res. 203, 67–74 (2012). source
• Supported

  The 11 C-(R)-PK11195 binding results (indexed under GLOSSARY; page not supplied) report significantly increased PET-tracer binding in a subgroup of patients with amnestic MCI compared with controls. The claim says activation was detected in patients with MCI, not in all patients, which matches the finding. (LLM, conf=0.93)

  cites [140] Okello, A. et al. Microglial activation and amyloid deposition in mild cognitive impairment: a PET study. Neurology 72, 56–62 (2009). source

In the paper

“Mechanismly, various factors, including genetics, amyloid protein, tau, ApoE, and neuroimmune activation, are involved in the pathogenesis of AD.”

What the sources say

• Supported

  The Amyloid section links genetic forms of AD and Aβ to pathogenesis and identifies tau accumulation as a downstream factor. The ApoE and Neuroimmune activation sections describe their roles in AD pathophysiology. Page numbers were not provided in the supplied passages. (LLM, conf=0.94)

  cites [123] Long, J. M. & Holtzman, D. M. Alzheimer disease: an update on pathobiology and treatment strategies. Cell 179, 312–339 (2019). source

In the paper

“Microglia in a homeostatic state use their ramified processes to survey the microenvironment in real time for potential signals that warrant further action.”

What the sources say

• Supported

  The Introduction (page not provided) describes mature microglia as constantly remodelling their processes and responding to signals in their extracellular environment. It also describes their physiological responses as dependent on the local environment, supporting the claim’s account of ongoing surveillance. (LLM, conf=0.88)

  cites [77] Tay, T. L., Savage, J. C., Hui, C. W., Bisht, K. & Tremblay, M. E. Microglia across the lifespan: from origin to function in brain development, plasticity and cognition. J. Physiol. 595, 1929–1945 (2017). source

In the paper

“On the other hand, microglia could also drive tau spreading and toxicity by promoting neuroinflammation, such as activating NACHT-, LRR- and pyrin (PYD)-domain-containing protein 3 (NLRP3) inflammasome155 or inducing NF-kB signaling.”

What the sources say

• Supported

  The Abstract identifies microglial NLRP3 activation as a driver of tau pathology. In “NLRP3 mediates Aβ-induced tau pathology,” the paper reports NLRP3-dependent tau seeding and hyperphosphorylation in mice; “NLRP3 regulates kinases and phosphatases” links microglial inflammasome activation to worsened tau pathology through IL-1β. The citation is attached to the NLRP3 example, not to the separate NF-κB example. (LLM, conf=0.89)

  cites [155] Ising, C. et al. NLRP3 inflammasome activation drives tau pathology. Nature 575, 669–673 (2019). source
• Supported

  The citation is offered for the NF-κB part of the sentence; the NLRP3 example has a separate citation. In the Discussion, the paper reports that microglial NF-κB activation accelerates tau spreading in PS19 mice and that its inhibition protects against tau-related toxicity and cognitive deficits. (LLM, conf=0.93)

  cites [156] Wang, C. et al. Microglial NF-kappaB drives tau spreading and toxicity in a mouse model of tauopathy. Nat. Commun. 13, 1969 (2022). source

In the paper

“However, its aggregation results in a gain of toxic function.”

What the sources say

• Supported

  Section 2 describes α-synuclein monomers aggregating into pathological oligomers and fibrils. Section 5 reports that oligomeric species are implicated in neuronal degeneration and that injected fibrils cause dopamine-neuron loss in mice. Together, these passages support the paraphrase that aggregation gives rise to toxic activity. (LLM, conf=0.88)

  cites [205] Bras, I. C. & Outeiro, T. F. Alpha-synuclein: mechanisms of release and pathology progression in synucleinopathies. Cells 10, 375 (2021). source

In the paper

“The extracellular lipid droplets directly decreased neuronal activity by increasing inward K+ currents.”

What the sources say

• Partly supported

  The paper’s main text (indexed under Abstract; no page supplied) says that APOE4 microglial conditioned medium is associated with increased neuronal inward K+ currents and reduced activity. It describes lipid droplets accumulating inside microglia, while increased cholesterol—not extracellular lipid droplets—is found in the medium; cholesterol exposure is proposed as a putative mechanism. The claim therefore identifies the wrong extracellular agent and overstates its direct effect. (LLM, conf=0.89)

  cites [197] Young, J. E. & Jayadev, S. Neighborhood matters: altered lipid metabolism in APOE4 microglia causes problems for neurons. Cell Stem Cell 29, 1159–1160 (2022). sourceExperimental — accuracy not yet measured

In the paper

“The uptake and processing of non-toxic α-syn by glia could lead to the generation of toxic strains specific to the disease through autophagy and impaired lysosomal degradation250”

What the sources say

• Supported

  The section “Glial Cells as Modulators of αSyn Toxicity in PD” explicitly proposes that glial uptake and processing of nontoxic αSyn could generate disease-specific toxic strains through autophagy and defective lysosomal degradation. The claim preserves the paper’s tentative wording. (LLM, conf=0.95)

  cites [250] Bartels, T., De Schepper, S. & Hong, S. Microglia modulate neurodegeneration in Alzheimer’s and Parkinson’s diseases. Science 370, 66–69 (2020). source

In the paper

“The byproduct of synthetic heroin, MPTP, could be taken up by dopaminergic neurons and induces parkinsonism in humans, non-human primates, and mice.”

What the sources say

• Partly supported

  The MPTP section reports PD-like effects in humans and nonhuman primates and parkinsonian motor deficits in mice. But its mechanism passage says MPTP is converted in astrocytes to MPP+, which is then taken up by dopaminergic neurons; it does not say MPTP itself is taken up. The paper describes synthetic meperidine contaminated with MPTP, rather than calling MPTP a byproduct of synthetic heroin. (LLM, conf=0.88)

  cites [232] Tieu, K. A guide to neurotoxic animal models of Parkinson’s disease. Cold Spring Harb. Perspect. Med. 1, a009316 (2011). sourceExperimental — accuracy not yet measured

In the paper

“LRRK2 (PARK8) gene mutations are the most common genetic cause of both familial and sporadic PD.257”

What the sources say

• Supported

  The Introduction explicitly identifies LRRK2 as PARK8 and states that its mutations are the most common genetic cause of both familial and sporadic PD. This directly matches the cited claim. (LLM, conf=0.95)

  cites [257] Li, J. Q., Tan, L. & Yu, J. T. The role of the LRRK2 gene in Parkinsonism. Mol. Neurodegener. 9, 47 (2014). source

In the paper

“TLR4 gene ablation in a transgenic mouse model of MSA with oligodendroglial α-syn overexpression impaired the phagocytic ability of microglia to α-syn, leading to enhanced motor impairment and augmented loss of nigrostriatal dopaminergic neurons.295”

What the sources say

• Supported

  Split into 2 atoms — 2 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  cites [295] Stefanova, N. et al. Toll-like receptor 4 promotes alpha-synuclein clearance and survival of nigral dopaminergic neurons. Am. J. Pathol. 179, 954–963 (2011). source

In the paper

“Microglial activation in middle frontal and superior or middle temporal gyrus regions was also highly found in vivo PET imaging studies in humans”

What the sources say

• Not checked yetcites [311] Turner, M. R. et al. Evidence of widespread cerebral microglial activation in amyotrophic lateral sclerosis: an [11C](R)-PK11195 positron emission tomography study. Neurobiol. Dis. 15, 601–609 (2004). source
• Partly supported

  The Results (Whole brain between-group analysis; page unavailable) report increased PET tracer binding in the motor cortices and corticospinal tract of patients with ALS. The Introduction also reports an earlier PET finding in the temporal cortex. Neither passage establishes the claimed high activation specifically in the middle frontal and superior or middle temporal gyri. (LLM, conf=0.83)

  cites [312] Zurcher, N. R. et al. Increased in vivo glial activation in patients with amyotrophic lateral sclerosis: assessed with [(11)C]-PBR28. Neuroimage Clin. 7, 409–414 (2015). sourceExperimental — accuracy not yet measured
• Partly supported

  The Results (Group level analysis; page unavailable) report significant PET-detected microglial activation in temporal cortex and premotor frontal cortex in people with SOD1-ALS. They do not identify the middle frontal or superior or middle temporal gyri specifically. The Results (Single-subject analysis; page unavailable) also say frontal-lobe clusters were less frequent in asymptomatic carriers, so the claim that activation was highly found in all the named regions overstates the findings. (LLM, conf=0.84)

  cites [313] Tondo, G. et al. (11) C-PK11195 PET-based molecular study of microglia activation in SOD1 amyotrophic lateral sclerosis. Ann. Clin. Transl. Neurol. 7, 1513–1523 (2020). sourceExperimental — accuracy not yet measured

In the paper

“Moreover, MSA mice with Tcrb (CD4 and CD8 T cell knockout) or Cd4 (CD4 T cell knockout) genetic deletion showed reduced inflammation and demyelination after exposure to syn301”

What the sources say

• Supported

  The Results section (‘Knockout of αβ T cells or CD4 T cells alone…’) identifies Tcrb−/− and Cd4−/− mice as the respective T-cell knockouts. After Olig001-SYN treatment, both showed reduced CNS myeloid activation and less demyelination than wild-type mice (Fig. 7). (LLM, conf=0.94)

  cites [301] Williams, G. P. et al. T cell infiltration in both human multiple system atrophy and a novel mouse model of the disease. Acta Neuropathol. 139, 855–874 (2020). source

In the paper

“However, neuron-specific expression of mSOD1 in transgenic mice failed to produce pathology or disease in these mice,328,329”

What the sources say

• Supported

  The Abstract reports no apparent motor deficit in the neuron-specific G37R mutant SOD1 mice up to 1.5 years of age and no significant motor-neuron cell death. The Discussion says these mice did not develop a neurodegenerative disease. The claim is supported for the mice and observation period studied. (LLM, conf=0.91)

  cites [328] Pramatarova, A., Laganiere, J., Roussel, J., Brisebois, K. & Rouleau, G. A. Neuron-specific expression of mutant superoxide dismutase 1 in transgenic mice does not lead to motor impairment. J. Neurosci. 21, 3369–3374 (2001). source
• Supported

  The Abstract reports that high-level expression and accumulation of mutant SOD1 in postnatal neurons produced no detectable pathology or disease in the transgenic mice. The transgenic-mouse section identifies the neuron-selective expression used in the study. (LLM, conf=0.94)

  cites [329] Lino, M. M., Schneider, C. & Caroni, P. Accumulation of SOD1 mutants in postnatal motoneurons does not cause motoneuron pathology or motoneuron disease. J. Neurosci. 22, 4825–4832 (2002). source

In the paper

“Nonsense or missense mutations in TREM2 have been identified in several families with FTD.343–345”

What the sources say

• Not checked yetcites [343] Le Ber, I. et al. Homozygous TREM2 mutation in a family with atypical frontotemporal dementia. Neurobiol. Aging 35, 2419 e2423–2419 e2425 (2014).
• Supported

  The Genetic Analysis results identify a nonsense TREM2 mutation (p.Q33X) and two missense mutations (p.T66M and p.Y38C) in three unrelated families. The Comment states that all three mutation carriers had a clinical diagnosis consistent with probable behavioral FTD, while noting atypical features; the paper describes their presentations as FTD-like. (LLM, conf=0.91)

  cites [344] Guerreiro, R. J. et al. Using exome sequencing to reveal mutations in TREM2 presenting as a frontotemporal dementia-like syndrome without bone involvement. JAMA Neurol. 70, 78–84 (2013). source
• Supported

  The Results (§3.2) identify a nonsense TREM2 mutation in affected members of a Colombian family, and the Introduction describes that family as having behavioral-variant frontotemporal lobar degeneration. This paper supports the nonsense-mutation example within the claim; the sentence cites multiple sources for the broader statement about several families. (LLM, conf=0.88)

  cites [345] Giraldo, M. et al. Variants in triggering receptor expressed on myeloid cells 2 are associated with both behavioral variant frontotemporal lobar degeneration and Alzheimer’s disease. Neurobiol. Aging 34, 2077 e2011–e2078 (2013). source

In the paper

“Also, transcriptomic and protein expression analyses of postmortem brain tissue in DLB did not reveal significant microglial activation.”

What the sources say

• Partly supported

  The Results (Microscopy) report elevated microglia-related transcripts in the DLB pulvinar, but no significant increase in the corresponding markers on histological protein analysis. The Discussion likewise notes immune-process transcript enrichment without corresponding protein-level evidence. Thus the claim captures the protein finding but overlooks the transcriptomic signal and generalizes a pulvinar finding to postmortem brain tissue in DLB. (LLM, conf=0.88)

  cites [419] Erskine, D. et al. Molecular changes in the absence of severe pathology in the pulvinar in dementia with Lewy bodies. Mov. Disord. 33, 982–991 (2018). sourceExperimental — accuracy not yet measured
• Not checked yetcites [423] Rajkumar, A. P. et al. Postmortem cortical transcriptomics of lewy body dementia reveal mitochondrial dysfunction and lack of neuroinflammation. Am. J. Geriatr. Psychiatry 28, 75–86 (2020). source

In the paper

“Furthermore, microglia could also phagocytize synapses that contain aggregated tau via synaptic tagging of C1q, leading to a decline in synapse density.390”

What the sources say

• Partly supported

  The Results (page unavailable) report C1q association with phospho-Tau-containing synapses, increased microglial engulfment in Tau-P301S mice, and a concurrent decline in synapse density. C1q-blocking antibodies also prevented synapse loss in neuron–microglia cultures. The paper does not establish that the engulfed synapses specifically contained aggregated tau; it identifies phosphorylated tau at synapses, which is not the same claim. (LLM, conf=0.86)

  cites [390] Dejanovic, B. et al. Changes in the synaptic proteome in tauopathy and rescue of tau-induced synapse loss by C1q antibodies. Neuron 100, 1322–1336.e1327 (2018). sourceExperimental — accuracy not yet measured

In the paper

“Genetic ablation of Cx3cl1396,397 or Cx3cr1389,398 in mouse models of tauopathy enhanced tau hyperphosphorylation, tau pathology, neuroinflammation, and cognitive deficits389,396–398 via IL-1/p38 MAPK pathway.”

What the sources say

• Supported

  The Discussion reports that CX3CR1-deficient hTau mice had enhanced microglial activation, tau hyperphosphorylation and pathology, and memory disturbances. It also links CX3CR1 deficiency to microglial IL-1, neuronal p38 MAPK activation, and tau phosphorylation. The sentence attaches separate citations to the Cx3cl1-ablation claim; this verdict concerns the Cx3cr1 claim supported by this paper. (LLM, conf=0.92)

  cites [389] Bhaskar, K. et al. Regulation of tau pathology by the microglial fractalkine receptor. Neuron 68, 19–31 (2010). source
• Partly supported

  The Results report increased AT8 tau phosphorylation, tau pathology, and inflammatory markers in hTau/Cx3cl1−/− mice; the cognitive-impairment Results report poorer learning than in hTau controls. The Background reports similar effects of Cx3cr1 deletion and links them to IL-1–p38 MAPK signaling. However, the Discussion says the pathway is *likely* involved, so the claim’s unqualified causal “via” overstates the evidence, particularly for Cx3cl1 deletion. (LLM, conf=0.87)

  cites [396] Bemiller, S. M. et al. Genetically enhancing the expression of chemokine domain of CX3CL1 fails to prevent tau pathology in mouse models of tauopathy. J. Neuroinflammation 15, 278 (2018). sourceExperimental — accuracy not yet measured
• Partly supported

  The MAPT-phosphorylation Results report increased phospho-MAPT after either Cx3cl1 or Cx3cr1 ablation, but this paper studied APPPS1 mice rather than a tauopathy model. The Discussion proposes IL-1/p38 MAPK signaling as a mechanism, while the paper attributes the hTau-model result to previous work; the cited passages do not report cognitive deficits. (LLM, conf=0.88)

  cites [397] Lee, S. et al. Opposing effects of membrane-anchored CX3CL1 on amyloid and tau pathologies via the p38 MAPK pathway. J. Neurosci. 34, 12538–12546 (2014). sourceExperimental — accuracy not yet measured
• Supported

  The citation is attached to the Cx3cr1 portion of the sentence, not the separately cited Cx3cl1 portion. The Discussion reports that Cx3cr1 deficiency in hTau mice increased tau hyperphosphorylation and aggregation, microglial activation, and memory impairment. The Introduction and Results link the tau effects to IL-1R–p38 MAPK signaling. Page numbers are unavailable in our copy. (LLM, conf=0.91)

  cites [398] Maphis, N. et al. Reactive microglia drive tau pathology and contribute to the spreading of pathological tau in the brain. Brain 138, 1738–1755 (2015). source

In the paper

“Furthermore, dose-dependent reductions of mHTT concentrations in CSF have been observed, with a 40% decrease in mHTT at the two highest medication dosages,530”

What the sources say

• Supported

  The “Concentrations of Mutant HTT in CSF” section reports dose-dependent reductions. Mean reductions were 42% and 38% at the two highest doses, 90 mg and 120 mg, respectively—approximately 40% each. No page number is provided in the supplied copy. (LLM, conf=0.94)

  cites [530] Tabrizi, S. J. et al. Targeting huntingtin expression in patients with Huntington’s disease. N. Engl. J. Med. 380, 2307–2316 (2019). source

In the paper

“Microglia also act as a mobile vehicle to propagate protein aggregates.”

In the paper

“Microglia activation is observed in various neurodegenerative diseases.”

• Also stated in: § Introduction · plain

  “Reactive microglia that refer to microglia undergoing morphological, molecular, and functional remodeling in response to brain challenges (i.e., amyloid β [Aβ] or α-synuclein [α-syn] deposition, infected, damaged, or degenerating neurons) have been observed in various neurodegenerative diseases.”

What the sources say

• Not checked yetcites [11] Savage, J. C., Carrier, M. & Tremblay, M. E. Morphology of microglia across contexts of health and disease. Methods Mol. Biol. 2034, 13–26 (2019). source
• Not checked yetcites [12] Bouvier, D. S. et al. High resolution dissection of reactive glial nets in Alzheimer’s disease. Sci. Rep. 6, 24544 (2016). source

In the paper

“Microglia both exert protective function by phagocytosing and clearing pathological protein aggregates”

What the sources say

• Not checked yetcites [2] Sarlus, H. & Heneka, M. T. Microglia in Alzheimer’s disease. J. Clin. Invest. 127, 3240–3249 (2017). source

In the paper

“Importantly, microglia dysfunction can be an active inducer of the initiation and progression of various neurodegenerative diseases.”

In the paper

“it is now well-established that microglia are derived from yolk sac (YS) erythromyeloid precursors (EMPs).”

What the sources say

• Not checked yetcites [42] Ginhoux, F. et al. Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 330, 841–845 (2010). source
• Not checked yetcites [43] Kierdorf, K. et al. Microglia emerge from erythromyeloid precursors via Pu.1- and Irf8-dependent pathways. Nat. Neurosci. 16, 273–280 (2013). source

In the paper

“Besides, fractalkine-dependent microglial pruning of OPCs is indispensable for proper myelination.”

What the sources say

• Not checked yetcites [119] Nemes-Baran, A. D., White, D. R. & DeSilva, T. M. Fractalkine-dependent microglial pruning of viable oligodendrocyte progenitor cells regulates myelination. Cell Rep. 32, 108047 (2020). source

In the paper

“recent developments in single-cell technologies have revealed multiple microglial states in human and mouse brains related to specific developmental, aging, and disease processes.”

What the sources say

• Not checked yetcites [4] Provenzano, F., Perez, M. J. & Deleidi, M. Redefining microglial identity in health and disease at single-cell resolution. Trends Mol. Med. 27, 47–59 (2021). source

In the paper

“Microglial activation is tightly regulated through receptor-ligand interactions, such as CX3CR1-CX3CL1 and SIRPa-CD47.”

What the sources say

• Not checked yetcites [79] Hanisch, U. K. & Kettenmann, H. Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat. Neurosci. 10, 1387–1394 (2007). source

In the paper

“The interaction between reactive microglia and astrocytes is critical in the development of neuroinflammation.”

In the paper

“Normal blood circulation is required for YS macrophage seeding of the CNS.”

What the sources say

• Not checked yetcites [42] Ginhoux, F. et al. Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 330, 841–845 (2010). source

In the paper

“AD patients all showed significantly increased regional TSPO ligand binding in the cortices compared to controls.”

What the sources say

• Not checked yetcites [134] Passamonti, L. et al. Neuroinflammation and functional connectivity in alzheimer’s disease: interactive influences on cognitive performance. J. Neurosci. 39, 7218–7226 (2019). source
• Not checked yetcites [135] Cagnin, A. et al. In-vivo measurement of activated microglia in dementia. Lancet 358, 461–467 (2001). source
• Not checked yetcites [136] Yokokura, M. et al. In vivo changes in microglial activation and amyloid deposits in brain regions with hypometabolism in Alzheimer’s disease. Eur. J. Nucl. Med. Mol. Imaging 38, 343–351 (2011). source

In the paper

“This observation supports the idea that the recruitment of YS progenitors into the brain is mediated by blood circulation.”

What the sources say

• Not checked yetcites [42] Ginhoux, F. et al. Fate mapping analysis reveals that adult microglia derive from primitive macrophages. Science 330, 841–845 (2010). source

In the paper

“EVs are essential mediators of microglia-astrocyte interaction.”

What the sources say

• Not checked yetcites [115] Bianco, F. et al. Astrocyte-derived ATP induces vesicle shedding and IL-1 beta release from microglia. J. Immunol. 174, 7268–7277 (2005). source

In the paper

“microglial activation was significantly higher within Aβ plaques compared with plaque-free cortical areas.”

What the sources say

• Not checked yetcites [125] Dal Bianco, A. et al. Multiple sclerosis and Alzheimer’s disease. Ann. Neurol. 63, 174–183 (2008). source
• Not checked yetcites [127] Liu, B. & Hong, J. S. Role of microglia in inflammation-mediated neurodegenerative diseases: mechanisms and strategies for therapeutic intervention. J. Pharmacol. Exp. Ther. 304, 1–7 (2003). source

In the paper

“Recently, genome-wide association studies (GWAS) have demonstrated that most AD risk genes are highly or exclusively in microglia”

What the sources say

• Not checked yetcites [124] Efthymiou, A. G. & Goate, A. M. Late onset Alzheimer’s disease genetics implicates microglial pathways in disease risk. Mol. Neurodegener. 12, 43 (2017). source

In the paper

“Thus, microglia play an indispensable role in regulating the formation, plasticity, and elimination of synapses throughout development and adulthood.”

In the paper

“scRNA-seq studies identified a specific microglial response state, called disease-associated microglia (DAMs), in mouse models and human patient specimens of AD.”

What the sources say

• Not checked yetcites [13] Keren-Shaul, H. et al. A unique microglia type associated with restricting development of Alzheimer’s disease. Cell 169, 1276–1290.e1217 (2017). source
• Not checked yetcites [14] Friedman, B. A. et al. Diverse brain myeloid expression profiles reveal distinct microglial activation states and aspects of Alzheimer’s disease not evident in mouse models. Cell Rep. 22, 832–847 (2018). source
• Not checked yetcites [16] Mathys, H. et al. Temporal tracking of microglia activation in neurodegeneration at single-cell resolution. Cell Rep. 21, 366–380 (2017). source

In the paper

“Moreover, distinct Aβ and tau-associated microglia signatures have been discovered in AD patients.”

What the sources say

• Not checked yetcites [15] Gerrits, E. et al. Distinct amyloid-beta and tau-associated microglia profiles in Alzheimer’s disease. Acta Neuropathol. 141, 681–696 (2021). source

In the paper

“Microglia play an essential role in the proper development and homeostasis of OPCs and oligodendrocytes.”

What the sources say

• Not checked yetcites [116] Hagemeyer, N. et al. Microglia contribute to normal myelinogenesis and to oligodendrocyte progenitor maintenance during adulthood. Acta Neuropathol. 134, 441–458 (2017). source

In the paper

“These findings suggest that microglia show plasticity when responding to various pathologies”

In the paper

“Microglia also play a crucial role in the modulation of synaptic plasticity.”

What the sources say

• Not checked yetcites [86] Rauti, R. et al. BDNF impact on synaptic dynamics: extra or intracellular long-term release differently regulates cultured hippocampal synapses. Mol. Brain 13, 43 (2020). source
• Not checked yetcites [87] Saw, G. et al. Epigenetic regulation of microglial phosphatidylinositol 3-kinase pathway involved in long-term potentiation and synaptic plasticity in rats. Glia 68, 656–669 (2020). source

In the paper

“Reactive microglia produce IL-1α, TNFα, and C1q, which induce the neurotoxic A1 astrocytes phenotype conversion.”

What the sources say

• Not checked yetcites [112] Liddelow, S. A. et al. Neurotoxic reactive astrocytes are induced by activated microglia. Nature 541, 481–487 (2017). source

In the paper

“Additionally, microglia could monitor and protect neuronal functions through microglia-neuron crosstalk.”

What the sources say

• Not checked yetcites [3] Cserep, C. et al. Microglia monitor and protect neuronal function through specialized somatic purinergic junctions. Science 367, 528–537 (2020). source

In the paper

“However, this simplistic classification fails to capture the complexity of microglial responses in the context of neurodegenerative disease.”

What the sources say

• Not checked yetcites [9] Colonna, M. & Butovsky, O. Microglia function in the central nervous system during health and neurodegeneration. Annu. Rev. Immunol. 35, 441–468 (2017). source
• Not checked yetcites [10] Guo, S., Wang, H. & Yin, Y. Microglia polarization from M1 to M2 in neurodegenerative diseases. Front. Aging Neurosci. 14, 815347 (2022). source

In the paper

“Similarly, with the presence of Aβ, TREM2-dependent activation of the DAM phenotype can also limit tau pathology propagation.”

In the paper

“These results suggest that microglia respond to the pathology of AD.”

In the paper

“In contrast, inhibiting microglia secretion of tau-containing EVs alleviated tau pathology and cognitive impairment in P301S tau transgenic mice161”

What the sources say

• Not checked yetcites [161] Ruan, Z. et al. P2RX7 inhibitor suppresses exosome secretion and disease phenotype in P301S tau transgenic mice. Mol. Neurodegener. 15, 47 (2020). source

In the paper

“Considerable evidence has found that microglia promote the uptake and degradation of Aβ.”

What the sources say

• Not checked yetcites [146] Heckmann, B. L. et al. LC3-associated endocytosis facilitates beta-amyloid clearance and mitigates neurodegeneration in murine Alzheimer’s disease. Cell 178, 536–551.e514 (2019). source

In the paper

“In AD mice, sustained microglial depletion with CSF1R inhibitor reduced plaque development.”

What the sources say

• Not checked yetcites [32] Ito, D. et al. Microglia-specific localisation of a novel calcium binding protein, Iba1. Brain Res. Mol. Brain Res. 57, 1–9 (1998). source

In the paper

“some studies have also found that the phagocytosis of Aβ by microglia promoted plaque development.”

What the sources say

• Not checked yetcites [152] Huang, Y. et al. Microglia use TAM receptors to detect and engulf amyloid beta plaques. Nat. Immunol. 22, 586–594 (2021). source

In the paper

“In MCI, microglial activation was positively correlated with amyloid load.”

What the sources say

• Not checked yetcites [141] Parbo, P. et al. Brain inflammation accompanies amyloid in the majority of mild cognitive impairment cases due to Alzheimer’s disease. Brain 140, 2002–2011 (2017). source
• Not checked yetcites [142] Parbo, P. et al. Does inflammation precede tau aggregation in early Alzheimer’s disease? A PET study. Neurobiol. Dis. 117, 211–216 (2018). source

In the paper

“In AD patients, snRNA-seq of the occipital cortex and the occipitotemporal cortex from AD patients and controls identified three clusters: homeostatic microglia, AD1-microglia, and AD2-microglia.”

In the paper

“The in vivo imaging study also found that microglial activation correlated with tau and amyloid in AD.”

What the sources say

• Not checked yetcites [143] Dani, M. et al. Microglial activation correlates in vivo with both tau and amyloid in Alzheimer’s disease. Brain 141, 2740–2754 (2018).

In the paper

“Astrocyte-derived IL-3 bound to the upregulated IL-3Rα in microglia, enhancing microglial migration toward Aβ deposits and the Aβ aggregates clearance.”

What the sources say

• Not checked yetcites [150] McAlpine, C. S. et al. Astrocytic interleukin-3 programs microglia and limits Alzheimer’s disease. Nature 595, 701–706 (2021). source

In the paper

“GWAS showed that the R47H variant of TREM2 was associated with a 2- to 4-fold increased risk for the development of AD.”

What the sources say

• Not checked yetcites [163] Guerreiro, R. et al. TREM2 variants in Alzheimer’s disease. N. Engl. J. Med. 368, 117–127 (2013). source
• Not checked yetcites [164] Jonsson, T. et al. Variant of TREM2 associated with the risk of Alzheimer’s disease. N. Engl. J. Med. 368, 107–116 (2013). source

In the paper

“Microglia limit Aβ-associated tau seeding and spreading in AD mouse models.”

In the paper

“TREM2-dependent microglial activation is critical to sustaining microglia defense against Aβ and tau pathology.”

In the paper

“The study found that microglial transcripts were most highly positively associated with tissue Aβ and tissue pTau density.”

What the sources say

• Not checked yetcites [145] Smith, A. M. et al. Diverse human astrocyte and microglial transcriptional responses to Alzheimer’s pathology. Acta Neuropathol. 143, 75–91 (2022). source

In the paper

“Besides, microglia facilitate Aβ spreading.”

What the sources say

• Not checked yetcites [153] Venegas, C. et al. Microglia-derived ASC specks cross-seed amyloid-beta in Alzheimer’s disease. Nature 552, 355–361 (2017). source
• Not checked yetcites [154] d’Errico, P. et al. Microglia contribute to the propagation of Abeta into unaffected brain tissue. Nat. Neurosci. 25, 20–25 (2022). source

In the paper

“Several other TREM2 variants that affect the expression of TREM2 also increased the risk of AD, including R62H, T66M, H157Y, and D87N.”

What the sources say

• Not checked yetcites [165] Roussos, P. et al. The triggering receptor expressed on myeloid cells 2 (TREM2) is associated with enhanced inflammation, neuropathological lesions and increased risk for Alzheimer’s dementia. Alzheimers Dement. 11, 1163–1170 (2015). source
• Not checked yetcites [166] Jin, S. C. et al. Coding variants in TREM2 increase risk for Alzheimer’s disease. Hum. Mol. Genet. 23, 5838–5846 (2014). source
• Not checked yetcites [167] Jiang, T. et al. A rare coding variant in TREM2 increases risk for Alzheimer’s disease in Han Chinese. Neurobiol. Aging 42, 217 e211–213 (2016). source
• Not checked yetcites [168] Olive, C. et al. Examination of the effect of rare variants in TREM2, ABI3, and PLCG2 in LOAD through multiple phenotypes. J. Alzheimers Dis. 77, 1469–1482 (2020). source

In the paper

“These reactive microglia were found to be clustered near Aβ plaques in various brain regions of AD mice and human postmortems.”

What the sources say

• Not checked yetcites [11] Savage, J. C., Carrier, M. & Tremblay, M. E. Morphology of microglia across contexts of health and disease. Methods Mol. Biol. 2034, 13–26 (2019). source
• Not checked yetcites [12] Bouvier, D. S. et al. High resolution dissection of reactive glial nets in Alzheimer’s disease. Sci. Rep. 6, 24544 (2016). source

In the paper

“The above evidence suggests that microglia-mediated neuroinflammation is detrimental in accelerating tau pathology.”

In the paper

“TREM2 knockout (KO) or TREM2 R47H variant dramatically enhanced tau seeding and spreading around plaques in AD mice.”

What the sources say

• Not checked yetcites [175] Gratuze, M. et al. Activated microglia mitigate Abeta-associated tau seeding and spreading. J. Exp. Med. 218, e20210542 (2021). source
• Not checked yetcites [176] Leyns, C. E. G. et al. TREM2 function impedes tau seeding in neuritic plaques. Nat. Neurosci. 22, 1217–1222 (2019). source
• Not checked yetcites [177] Lee, S. H. et al. Trem2 restrains the enhancement of tau accumulation and neurodegeneration by beta-amyloid pathology. Neuron 109, 1283–1301.e1286 (2021). source

In the paper

“Microglia in the SN of PD patients showed a higher proportion of amoeboid morphology, which is indicative of a reactive state.”

What the sources say

• Not checked yetcites [215] Smajic, S. et al. Single-cell sequencing of human midbrain reveals glial activation and a Parkinson-specific neuronal state. Brain 145, 964–978 (2022). source

In the paper

“Genetic elimination of the fibrinogen binding motif to CD11b ameliorated the above pathological processes and cognitive impairments.”

What the sources say

• Not checked yetcites [200] Merlini, M. et al. Fibrinogen induces microglia-mediated spine elimination and cognitive impairment in an Alzheimer’s disease model. Neuron 101, 1099–1108.e1096 (2019). source

In the paper

“Monocytes and macrophages have been found to infiltrate the inflamed brain.”

In the paper

“higher CSF sTREM2/p-Tau was associated with slower cognitive decline”

What the sources say

• Not checked yetcites [188] Ewers, M. et al. Increased soluble TREM2 in cerebrospinal fluid is associated with reduced cognitive and clinical decline in Alzheimer’s disease. Sci. Transl. Med. 11, eaav6221 (2019). source

In the paper

“Microglia harboring an APOE4 allele showed altered cellular metabolism, increasing intracellular and extracellular lipid accumulation.”

What the sources say

• Not checked yetcites [197] Young, J. E. & Jayadev, S. Neighborhood matters: altered lipid metabolism in APOE4 microglia causes problems for neurons. Cell Stem Cell 29, 1159–1160 (2022). source

In the paper

“Selective removal of astrocytic APOE4 decreased microglial phagocytosis of synaptic elements in the tau transgenic mouse model.”

What the sources say

• Not checked yetcites [96] Wang, C. et al. Selective removal of astrocytic APOE4 strongly protects against tau-mediated neurodegeneration and decreases synaptic phagocytosis by microglia. Neuron 109, 1657–1674.e1657 (2021). source

In the paper

“Increased expression of proteins associated with non-microglia myeloid cells, such as CD163, has been observed in the brains of PD patients.”

What the sources say

• Not checked yetcites [227] Pey, P., Pearce, R. K., Kalaitzakis, M. E., Griffin, W. S. & Gentleman, S. M. Phenotypic profile of alternative activation marker CD163 is different in Alzheimer’s and Parkinson’s disease. Acta Neuropathol. Commun. 2, 21 (2014). source

In the paper

“Other microglial activation markers, such as pro-inflammatory enzymes like iNOS and COX211,212 and phagocytosis-associated marker CD68,213 were also upregulated in PD patients.”

What the sources say

• Not checked yetcites [211] Hunot, S. et al. Nitric oxide synthase and neuronal vulnerability in Parkinson’s disease. Neuroscience 72, 355–363 (1996). source
• Not checked yetcites [212] Knott, C., Stern, G. & Wilkin, G. P. Inflammatory regulators in Parkinson’s disease: iNOS, lipocortin-1, and cyclooxygenases-1 and -2. Mol. Cell. Neurosci. 16, 724–739 (2000). source
• Not checked yetcites [213] Doorn, K. J. et al. Microglial phenotypes and toll-like receptor 2 in the substantia nigra and hippocampus of incidental Lewy body disease cases and Parkinson’s disease patients. Acta Neuropathol. Commun. 2, 90 (2014).

In the paper

“High CSF sTREM2 was associated with slower rates of Aβ accumulation”

What the sources say

• Not checked yetcites [187] Ewers, M. et al. Higher CSF sTREM2 and microglia activation are associated with slower rates of beta-amyloid accumulation. EMBO Mol. Med. 12, e12308 (2020). source

In the paper

“The microglial activation and recruitment (microgliosis) process is accompanied by increased cytokine levels.”

What the sources say

• Not checked yetcites [220] Imamura, K. et al. Distribution of major histocompatibility complex class II-positive microglia and cytokine profile of Parkinson’s disease brains. Acta Neuropathol. 106, 518–526 (2003). source

In the paper

“Additionally, PET scans of PD patients revealed widespread microglial activation.”

What the sources say

• Not checked yetcites [214] Gerhard, A. et al. In vivo imaging of microglial activation with [11C](R)-PK11195 PET in idiopathic Parkinson’s disease. Neurobiol. Dis. 21, 404–412 (2006). source

In the paper

“Microglia could also lead to synaptic dysfunction in vivo and in vitro by releasing Aβ-containing EVs.”

What the sources say

• Not checked yetcites [198] Gabrielli, M. et al. Microglial large extracellular vesicles propagate early synaptic dysfunction in Alzheimer’s disease. Brain 145, 2849–2868 (2022). source

In the paper

“The study also revealed that the reactive microglia states are enriched in cytokine secretion and the stress response to unfolded protein pathways.”

What the sources say

• Not checked yetcites [215] Smajic, S. et al. Single-cell sequencing of human midbrain reveals glial activation and a Parkinson-specific neuronal state. Brain 145, 964–978 (2022). source

In the paper

“a specific type of microglia, known as Cspg4-expressing microglia, has been identified as having the ability to proliferate triggered by pathological α-syn during neurodegeneration, particularly in PD.”

What the sources say

• Not checked yetcites [219] Liu, Y. J. et al. Cspg4(high) microglia contribute to microgliosis during neurodegeneration. Proc. Natl Acad. Sci. USA 120, e2210643120 (2023). source

In the paper

“The E4 allele of APOE increases the risk of developing late-onset AD.”

What the sources say

• Not checked yetcites [196] Scheltens, P. et al. Alzheimer’s disease. Lancet 397, 1577–1590 (2021). source

In the paper

“Through snRNA-seq analysis of frozen midbrain tissue from PD patients and controls, seven distinct microglia subpopulations were identified based on the expression of specific marker genes.”

What the sources say

• Not checked yetcites [215] Smajic, S. et al. Single-cell sequencing of human midbrain reveals glial activation and a Parkinson-specific neuronal state. Brain 145, 964–978 (2022). source

In the paper

“Notably, the impact of TREM2 on Aβ and tau pathology may vary at different disease stages.”

In the paper

“Elevated levels of cytokines (including IL1β, IL2, IL6, IFNγ, and TNFα) and CD4+ lymphocytes have been detected in both serum and CSF of PD patients.”

What the sources say

• Not checked yetcites [221] Nagatsu, T., Mogi, M., Ichinose, H. & Togari, A. Cytokines in Parkinson’s disease. J. Neural Transm. Suppl. 58, 143–151 (2000).
• Not checked yetcites [222] Schroder, J. B. et al. Immune cell activation in the cerebrospinal fluid of patients with Parkinson’s disease. Front. Neurol. 9, 1081 (2018). source

In the paper

“In rats, 6-OHDA injection also causes reactive microgliosis, which precedes astrogliosis and dopaminergic cell death.”

What the sources say

• Not checked yetcites [234] Marinova-Mutafchieva, L. et al. Relationship between microglial activation and dopaminergic neuronal loss in the substantia nigra: a time course study in a 6-hydroxydopamine model of Parkinson’s disease. J. Neurochem. 110, 966–975 (2009). source

In the paper

“mutations in SNCA have been proposed to cause aberrant conformation in α-syn, resulting in enhanced conversion of soluble α-syn into insoluble aggregates identified in PD.”

What the sources say

• Not checked yetcites [256] Blauwendraat, C., Nalls, M. A. & Singleton, A. B. The genetic architecture of Parkinson’s disease. Lancet Neurol. 19, 170–178 (2020). source

In the paper

“An increase in the macrophages, specifically CD163+ macrophages was also detected in the area of neurodegeneration in rodent PD models.”

What the sources say

• Not checked yetcites [228] Tentillier, N. et al. Anti-inflammatory modulation of microglia via CD163-targeted glucocorticoids protects dopaminergic neurons in the 6-OHDA Parkinson’s disease model. J. Neurosci. 36, 9375–9390 (2016). source

In the paper

“When α-syn accumulates outside of cells and is not properly cleared, it can activate microglia through PRRs, leading to the release of inflammatory cytokines.”

What the sources say

• Not checked yetcites [9] Colonna, M. & Butovsky, O. Microglia function in the central nervous system during health and neurodegeneration. Annu. Rev. Immunol. 35, 441–468 (2017). source

In the paper

“Oligomeric α-syn directly engages TLR1/2 and TLR4 to induce a pro-inflammatory M1 phenotype.”

What the sources say

• Not checked yetcites [246] Fellner, L. et al. Toll-like receptor 4 is required for alpha-synuclein dependent activation of microglia and astroglia. Glia 61, 349–360 (2013). source
• Not checked yetcites [247] Kim, C. et al. Neuron-released oligomeric alpha-synuclein is an endogenous agonist of TLR2 for paracrine activation of microglia. Nat. Commun. 4, 1562 (2013). source

In the paper

“These findings suggest that peripheral adaptive immunity might indirectly contribute to microglial activation during the neurodegenerative process in PD.”

In the paper

“Remarkably, neuroinflammation induced by α-syn may occur even before the loss of dopaminergic neurons in PD.”

What the sources say

• Not checked yetcites [237] Allen Reish, H. E. & Standaert, D. G. Role of alpha-synuclein in inducing innate and adaptive immunity in Parkinson disease. J. Parkinsons Dis. 5, 1–19 (2015). source

In the paper

“Remarkably, reactive M1 microglia were found several years after MPTP exposure in humans and non-human primates exposed to MPTP, indicating a long-lasting reactive microgliosis.”

What the sources say

• Not checked yetcites [233] McGeer, P. L. & McGeer, E. G. Glial reactions in Parkinson’s disease. Mov. Disord. 23, 474–483 (2008). source

In the paper

“The CCL2-CCR2 axis has been implicated in the infiltration of monocytes into the inflamed brain.”

What the sources say

• Not checked yetcites [229] Gliem, M., Schwaninger, M. & Jander, S. Protective features of peripheral monocytes/macrophages in stroke. Biochim. Biophys. Acta 1862, 329–338 (2016). source

In the paper

“These findings suggest that LRRK2 may primarily modulate the innate immune system and inflammation in PD.”

In the paper

“Microglia have pattern recognition receptors (PRRs) such as TLRs, nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), and scavenger receptors (SRs) that enable them to detect and respond to different stimuli, including extracellular α-syn.”

In the paper

“Overall, CD163+ and CCR2+ monocytes appear to contribute to neurodegeneration in PD both through peripheral actions and infiltrating the brain.”

In the paper

“Subsequent investigations of postmortem brain tissue from PD patients revealed that reactive microglia, characterized by amoeboid-shaped morphology, were associated with α-syn pathology in the SN and hippocampus.”

What the sources say

• Not checked yetcites [220] Imamura, K. et al. Distribution of major histocompatibility complex class II-positive microglia and cytokine profile of Parkinson’s disease brains. Acta Neuropathol. 106, 518–526 (2003). source

In the paper

“CD36 and P2X7 receptors are also involved in microglial activation induced by α-syn.”

What the sources say

• Not checked yetcites [248] Su, X., Federoff, H. J. & Maguire-Zeiss, K. A. Mutant alpha-synuclein overexpression mediates early proinflammatory activity. Neurotox. Res. 16, 238–254 (2009). source
• Not checked yetcites [249] Crabbe, M. et al. Increased P2X7 receptor binding is associated with neuroinflammation in acute but not chronic rodent models for Parkinson’s disease. Front. Neurosci. 13, 799 (2019). source

In the paper

“Research on microglia has shown that TLR2 or TLR4 stimulation can increase the expression and phosphorylation of LRRK2.259,260”

What the sources say

• Not checked yetcites [259] Moehle, M. S. et al. LRRK2 inhibition attenuates microglial inflammatory responses. J. Neurosci. 32, 1602–1611 (2012). source
• Not checked yetcites [260] Schapansky, J., Nardozzi, J. D., Felizia, F. & LaVoie, M. J. Membrane recruitment of endogenous LRRK2 precedes its potent regulation of autophagy. Hum. Mol. Genet. 23, 4201–4214 (2014). source

In the paper

“However, microglial activation in the brain of PD patients was not significantly associated with peripheral inflammation markers.”

What the sources say

• Not checked yetcites [231] Liu, S. Y. et al. Brain microglia activation and peripheral adaptive immunity in Parkinson’s disease: a multimodal PET study. J. Neuroinflammation 19, 209 (2022). source

In the paper

“which suggests that microglial activation likely promotes neurodegeneration in MSA.”

What the sources say

• Not checked yetcites [283] Ishizawa, K. et al. Microglial activation parallels system degeneration in multiple system atrophy. J. Neuropathol. Exp. Neurol. 63, 43–52 (2004). source

In the paper

“They found that high-ordered oligomers rather than monomers induced microglial activation identified by both morphological changes from bipolar to amoeboid and biochemical activation profiles manifested with increased pro-inflammatory cytokines secretion.294”

What the sources say

• Not checked yetcites [294] Daniele, S. G. et al. Activation of MyD88-dependent TLR1/2 signaling by misfolded alpha-synuclein, a protein linked to neurodegenerative disorders. Sci. Signal 8, ra45 (2015). source

In the paper

“PET imaging also demonstrated microglial activation in the brains of patients with MSA.”

What the sources say

• Not checked yetcites [286] Kubler, D. et al. Widespread microglial activation in multiple system atrophy. Mov. Disord. 34, 564–568 (2019). source
• Not checked yetcites [287] Jucaite, A. et al. Glia imaging differentiates multiple system atrophy from parkinson’s disease: a positron emission tomography study with [(11) C]PBR28 and Machine Learning Analysis. Mov. Disord. 37, 119–129 (2022). source

In the paper

“observed a conspicuous pattern of increased microglial activation in the cerebellar white matter and lentiform nucleus in MSA compared with PD.287”

What the sources say

• Not checked yetcites [287] Jucaite, A. et al. Glia imaging differentiates multiple system atrophy from parkinson’s disease: a positron emission tomography study with [(11) C]PBR28 and Machine Learning Analysis. Mov. Disord. 37, 119–129 (2022). source

In the paper

“A significant constituent of GCI is insoluble α-syn.”

What the sources say

• Not checked yetcites [289] Trojanowski, J. Q., Revesz, T. & Neuropathology Working Group on, M. S. A. Proposed neuropathological criteria for the post mortem diagnosis of multiple system atrophy. Neuropathol. Appl. Neurobiol. 33, 615–620 (2007). source

In the paper

“In microglia, the knockdown of DJ-1 has been shown to enhance the production of inflammatory cytokines in response to LPS.263”

What the sources say

• Not checked yetcites [263] Lin, Z. et al. DJ-1 inhibits microglial activation and protects dopaminergic neurons in vitro and in vivo through interacting with microglial p65. Cell Death Dis. 12, 715 (2021). source

In the paper

“The results showed significant widespread microgliosis in both neocortex and white matter in MSA patients compared with controls.284,285”

What the sources say

• Not checked yetcites [284] Salvesen, L. et al. Neocortical neuronal loss in patients with multiple system atrophy: a stereological study. Cereb. Cortex 27, 400–410 (2017).
• Not checked yetcites [285] Nykjaer, C. H., Brudek, T., Salvesen, L. & Pakkenberg, B. Changes in the cell population in brain white matter in multiple system atrophy. Mov. Disord. 32, 1074–1082 (2017). source

In the paper

“The pathological hallmark of MSA is the abnormal accumulation of α-syn in the cytoplasm of oligodendrocytes, named glial cytoplasmic inclusions (GCIs).271–275”

What the sources say

• Not checked yetcites [271] Papp, M. I., Kahn, J. E. & Lantos, P. L. Glial cytoplasmic inclusions in the CNS of patients with multiple system atrophy (striatonigral degeneration, olivopontocerebellar atrophy and Shy-Drager syndrome). J. Neurol. Sci. 94, 79–100 (1989). source
• Not checked yetcites [272] Tu, P. H. et al. Glial cytoplasmic inclusions in white matter oligodendrocytes of multiple system atrophy brains contain insoluble alpha-synuclein. Ann. Neurol. 44, 415–422 (1998). source
• Not checked yetcites [273] Cykowski, M. D. et al. Expanding the spectrum of neuronal pathology in multiple system atrophy. Brain 138, 2293–2309 (2015). source
• Not checked yetcites [274] Nishie, M., Mori, F., Yoshimoto, M., Takahashi, H. & Wakabayashi, K. A quantitative investigation of neuronal cytoplasmic and intranuclear inclusions in the pontine and inferior olivary nuclei in multiple system atrophy. Neuropathol. Appl. Neurobiol. 30, 546–554 (2004). source
• Not checked yetcites [275] Yokoyama, T., Kusunoki, J. I., Hasegawa, K., Sakai, H. & Yagishita, S. Distribution and dynamic process of neuronal cytoplasmic inclusion (NCI) in MSA: correlation of the density of NCI and the degree of involvement of the pontine nuclei. Neuropathology 21, 145–154 (2001). source